J Orthopaed Traumatol (2013) 14:5157

DOI 10.1007/s10195-012-0218-7

ORIGINAL ARTICLE

Can a combination of different risk factors be correlated with leg

fracture healing time?
Leo Massari Francesco Falez Vincenzo Lorusso Giacomo Zanon
Luigi Ciolli Filippo La Cava Matteo Cadossi Eugenio Chiarello
Francesca De Terlizzi Stefania Setti Francesco Maria Benazzo

Received: 5 February 2012 / Accepted: 21 October 2012 / Published online: 22 November 2012
The Author(s) 2012. This article is published with open access at Springerlink.com

Abstract
Background A multicenter retrospective analysis of
patients treated for leg fractures was conducted to develop
a score that correlates with fracture healing time and to
identify the risk gradient for delayed healing.
Methods Fifty-three patients were analyzed and considered healed when full weight bearing was possible. Patients
were divided into those who healed within 180 days and
those who took longer to heal. Risk factors associated with
delayed healing, fracture morphology, and orthopedic
treatments were recorded. The available literature was used
to weight the relative risk associated with each factor;
values were combined into a score evaluating the risk of
delayed healing: L-ARRCO (a literature-based score where

L. Massari
V. Lorusso
Orthopaedic and Traumatology Department, SantAnna
Hospital, University of Ferrara, Via Savonarola 9,
44121 Ferrara, Italy
F. Falez
L. Ciolli
F. La Cava
Orthopaedic and Traumatology Department, S. Spirito in Sassia
Hospital, Lungotevere in Sassia 1, 00193 Rome, Italy
G. Zanon
F. M. Benazzo
Orthopaedic and Traumatology Department, IRCCS Foundation
San Matteo Hospital, University of Pavia, Viale Camillo Golgi
19, 27100 Pavia, Italy
M. Cadossi (&)
E. Chiarello
II Orthopaedic and Traumatology Clinic, Rizzoli Orthopaedic
Institute, University of Bologna, Via Pupilli 1, 40134 Bologna,
BO, Italy
e-mail: matteocadossi@hotmail.com
F. De Terlizzi
S. Setti
IGEA SpA, Clinical Biophysics, Via Parmenide 10/A,
41012 Carpi, MO, Italy

the risk of delayed bone healing is calculated using a

specific algorithm). Other risk factors associated with
delayed healing were then considered in order to calculate
a new score, ARRCO. Continuous variables were compared between groups using Students heteroschedastic
two-tail t test. Receiver operating characteristic (ROC)
curves and the areas under the curves were calculated to
determine the ability of this score to discriminate subjects
with delayed healing.
Results The mean L-ARRCO scores of the patients who
healed within and after 180 days were significantly different (5.78 1.59 and 7.05 2.46, respectively). The
mean ARRCO scores of the patients who healed within
and after 180 days were also significantly different
(5.92 1.78 and 9.03 2.79, respectively). However, the
area under the ROC curve was significantly smaller
for L-ARRCO than for ARRCO (0.62 0.09 versus
0.82 0.07).
Conclusions The ARRCO score is significantly associated with fracture healing time and could be used to
identify fractures at risk, allowing early intervention to
stimulate osteogenesis.
Keywords
score

Leg fracture
Delayed healing
Risk factor

Introduction
Fracture healing begins immediately after the traumatic
event and continues until reconstitution of the mechanical
competence of the bone is complete. For leg fractures, this
process is normally completed within 34 months, but can
take six months or longer [13]. It is estimated that 13 %
of tibia fractures present delayed healing [4]. This

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complication involves a prolonged period of functional

limitation and delayed rehabilitation, and can require surgery to reactivate and finalize the bone repair process.
Early identification of fractures that may be at risk of
delayed healing would be advantageous to patients, and
would allow early intervention, leading to a significant
reduction in social health costs. Several clinical studies
have identified a series of factors associated with the risk of
prolonged healing time for fractures. However, no effective
and reliable procedures exist for the early identification of a
fracture at high risk of delayed healing. Identified risk
factors are related to: (1) the patients clinical history,
including age [5], gender [6, 7], smoking habit [6, 8, 9],
diabetes [10], and alcoholism [11]; (2) the morphology of
the fracture including the site [6, 7, 10, 1214], diastasis of
the stumps [15, 16], the presence of a skin lesion and its
degree [15, 1721], and the fracture mechanism [15, 22];
(3) the treatment of the fracture, including the synthesis
device [4] and the duration of surgical intervention [4].
The majority of clinical studies have identified these risk
factors using a univariate model of statistical analysis, but
this does not take into account the interdependence of the
factors considered. Attempts to assess the importance and
interdependence of the various risk factors in a multivariate
model are restricted to a small number of examples; the
authors focus their analysis onto characteristics of the
fracture and neglect patient history factors, as reported by
Audige et al. [4] in a retrospective study and by Hee et al.
[5] in a prospective study. Nevertheless, there is currently
no score that is calculated at the time of fracture which
could provide an estimate of the time required for the
fracture to heal or the gradient of risk that the fracture will
result in delayed union.
In this study, clinical records from patients treated for
leg fractures were reviewed to collect detailed information
concerning patient history risk factors, fracture morphology, and orthopedic treatment. Various factors were combined in the ARRCO score (where the risk of delayed bone
healing is calculated using a specific algorithm) as proof of
the principle that a score can be correlated with healing
time.

Orthopedic and Traumatology Department, Santo Spirito in

Sassia Hospital, Rome.
Inclusion criteria were: signed informed consent to
collect clinical data; leg fractures treated conservatively
and/or surgically. Exclusion criteria were: osteoporosis; leg
fractures involving the tibial plateau; and isolated fractures
of the malleolus.
The study was authorized by the local ethical committees and was performed in accordance with the ethical
standards of the 1964 Declaration of Helsinki as revised in
2000.

Materials and methods

Statistical analysis (level of significance

set at p \ 0.05)

Data collection
Data contained in each patients record were recorded in an
electronic case report form (e-CRF) that was created
especially for this study and developed using object-oriented C# programming and the Microsoft.Net 2.0 Framework. Table 1 presents the information collected on patient
history risk factors and the morphology and treatment of
the fracture.
As this was a retrospective study, X-ray controls were
not always available. Therefore, clinical healing of the
patient was considered the end-point. Patients were classed
as healed when there was no further limitation to limb
function and no further radiographic or clinical controls
were required to confirm effective healing of the fracture.
Patients were considered clinically healed when full
weight-bearing was allowed without support and pain.
L-ARRCO was calculated, where L indicates the
exclusive employment of parameters identified in the
literature as being associated with prolonged healing time.
Each of the parameters was assigned a score ranging from
zero to four as a function of the RR (relative risk) value
[4, 5, 17, 18], as demonstrated in Table 2. The L-ARRCO
score reached a maximum of 20 and was the sum of the
scores assigned to each risk factor.
In a second analysis, all parameters collected in the
e-CRF were considered and their association with prolonged healing time was calculated using logistic analysis
(RR). A second algorithm, ARRCO, whose values ranged
from 0 to 26, was calculated.

Patients
Ninety-three patients treated for leg fractures were analyzed retrospectively between 2007 and 2009 at three
orthopedic centers: the Orthopedic and Traumatology
Department, SantAnna Hospital, University of Ferrara; the
Orthopedic and Traumatology Department, IRCCS Foundation San Matteo Hospital, University of Pavia; the

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Statistical analysis was performed using SPSS 15.0 software (SPSS Inc., Chicago, IL, USA). The characteristics of
the population analyzed were described by calculating the
mean value, standard deviation, and maximum and minimum values.
To conduct univariate logistic analysis to determine the
RRs, delayed healing was attributed to a patient who had

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Table 1 Patient risk factors

Patient history
factors

Age; sex; height; weight; smoking status (amount and since when); diabetes; malnutrition; abuse (alcohol, narcotics, etc.);
drugs used (antibiotics, NSAIDs, corticosteroids, other, specifying the active principle and dosage); associated
pathologies; previous surgery

Fracture
morphology

Date of trauma; site (tibia, fibia, tibia and fibia), level (proximal or distal), and lesion zone (epiphysis, metaphysis,
diaphysis); side of fracture (right or left); AO classification; type of trauma (high/low energy, details on origin of trauma);
type of fracture (closed, exposed \5 cm, exposed [5 cm, open grade I); loss of bone (and details); associated lesions
(cutaneous, nervous, tendon, muscular, vascular, none, others); blood loss and hemoglobin value in blood; previous
interventions at lesion site (and details); presence of synthesis device at time of trauma; alignment, stability and diastasis
between stumps (2, 4, 6, 8, 10 mm) before treatment
Date of orthopedic treatment; treatment (surgical or conservative); conservative treatment details (cast, brace, other);
surgical treatment details (mini-invasive surgery); synthesis device (external fixator, endomedullary nail, plate, locking
compression plate, other); further treatment for stabilization (cast, brace, other, none); treatment with autologous bone
grafts, homoplastic grafts, stem cells, mesenchymal cells, saw bone, platelet gel, other, none; length of surgery (\200 or
[200 min); intraoperative complications (cutaneous, nervous, tendon, vascular, bone, none, other); blood loss and
hemoglobin count; complications immediately after operation (24 h); administration of drugs after treatment (antibiotics,
NSAIDs, corticosteroids, other, specifying active principle and dosage); thrombo-embolism prophylaxis; alignment,
stability and minimum diastasis between stumps (2, 4, 6, 8, 10 mm) after treatment; biophysical therapy (details, start
date) at follow-up; drugs used at follow-up (antibiotics, NSAIDs, corticosteroids, other, specifying active principle and
dosage); infection at follow-up; removal of fixing device at follow-up; removal of fixing device at follow-up; new
treatment (surgical or conservative) at follow-up at the lesion site; re-fracture at follow-up at the lesion site; alignment,
stability and minimum diastasis between stumps (2, 4, 6, 8, 10 mm) at follow-up; clinical healing at follow-up (patient
has no functional limitation)

Treatment of
fracture

Table lists the data collected concerning the risk factors for patients selected during 20072009 at the three orthopedic centers enrolled in the
study

not attained clinical healing at 180 days, as previously

defined.
The correlation between score and healing time was
calculated using the linear regression test and Spearmans
correlation coefficient. Continuous variables were compared between the two groups using Students heteroschedastic two-tail t test.
Analysis by ROC (receiver operating characteristic)
curve and calculation of the area under the curve (AUC)
was used to determine the ability of the score to discriminate subjects with delayed healing from others. Each point
on the curve represents a threshold value of the analyzed
score for which the sensitivity and specificity can be calculated. The sensitivity of the test is the percentage of
pathological subjects correctly identified by the method
with respect to the whole group of pathological subjects;
the specificity is the percentage of healthy subjects correctly identified as healthy with respect to the group of
effectively healthy subjects.

Results
Of the 93 patients, the information required to complete the
e-CRF was available for 53 individuals (38 male, 15
female). The characteristics of these subjects are summarized in Table 3. For 47 patients, the fracture was treated
with a single surgical operation; the remaining patients
underwent a second operation.

Analysis of correlation with healing time

The L-ARRCO score was calculated for each patient. The
Pearson coefficient of correlation between the L-ARRCO
score and clinical healing time was positive, with a value
r = ?0.400, p = 0.003 (Fig. 1).
In the group of patients analyzed, 36 attained clinical
healing within 180 days, and 17 were defined as patients
with delayed healing. The mean value of the L-ARRCO
score for patients who healed within 180 days was
5.78 1.59 (CI 5.246.31), and that for the patients who
healed after 180 days was 7.05 2.46 (CI 5.738.03),
p = 0.044. Figure 2 shows the score distributions for the
two groups. This first analysis demonstrates that patients
with an L-ARRCO score of between four and six had
healing times ranging from 44 to 302 days. Therefore, the
analysis was focused on these groups of patients to identify
other risk factors not included in the L-ARRCO score that
limit the specificity and sensitivity of the score.
Using the univariate logistic model, factors with a significant relative risk value, p = 0.05, were identified
(Table 4). These factors were used to calculate the ARRCO
score for each patient. The linear correlation between the
ARRCO score and the clinical healing time was analyzed
(Fig. 3). The Pearson correlation coefficient was positive,
?0.690, p \ 0.0001significantly higher than that previously obtained (p \ 0.0001).
The mean value of the ARRCO score for patients who
healed within 180 days was 5.92 1.78 (CI 5.316.52),

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Table 2 Risk factors used for the L-ARRCO score

Risk factor

L-ARRCO score

Importantly, for 70 % specificity values, a sensitivity of

82 % was achieved with the ARRCO score, whereas only
41 % sensitivity was achieved with the L-ARRCO score.

Patient history factors

Age
\46

4660

[60

Obesity

Smoking status

Use of NSAID

Use of steroids

Diabetes

Discussion

Fracture morphology and orthopedic treatment

Type of fracture
Closed

Exposed \ 5 cm

Exposed [ 5 cm

Open grade I

Localization
Diaphysis

Epiphysis-metaphysis

Treatment
Conservative

Plate

Endomedullary nail

External fixator

Alignment

Stability

Diastasis

Table provides a description of the risk factors used to calculate the

L-ARRCO score

Table 3 Patient characteristics

Age (years)
Height (cm)

Mean

SD

46.4

21.3

17

95

150

188

171

Min

Max

Weight (kg)

71.9

13.4

30

105

24.6

3.7

13

33

BMI (kg/m )

Table shows anagraphic and anthropometric data for the 53 subjects

considered

and that for patients who healed after 180 days was
9.03 2.79 (CI 7.5510.33), p \ 0.0001 (Fig. 4).
In the discrimination analysis between subjects who
healed within 180 days and those who took longer than
180 days, the ROC curve with the ARRCO score gave
an AUC that was significantly greater (0.82 0.07, CI
0.690.96) than that obtained with the L-ARRCO
score (0.62 0.09, CI 0.460.79), p \ 0.0001 (Fig. 5).

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It is difficult to assess whether, and with what probability, a

fracture will evolve into delayed union or a failed union,
often preventing early action that could be taken to
enhance healing. It is only a posteriori (i.e., after the onset
of the complication) that evidence of a series of risk factors
that could not be immediately identified at the time of
trauma or immediately following treatment (whether surgical or conservative) can be identified. There are no reliable clinical or laboratory investigations that can identify
fractures at risk (so-called because they require a prolonged time to heal).
Various studies have demonstrated that a high-energy
trauma, loss of bone and cutaneous substance, associated
nerve and vascular lesions, the co-presence of diseases
such as diabetes, and smoking are all factors that contribute
to prolonged healing time of a fracture [4]. The associated
RR has been calculated for each of these factors, but they
have not been combined to obtain a risk gradient with good
sensitivity and specificity that could find valid clinical
application [4, 5, 17, 18].
In the present work, the L-ARRCO score was developed
by combining the parameters reported in the literature
[48, 1022] and tested on a group of patients treated for
leg fractures to assess its correlation with healing time. The
decision to confine this investigation to the leg alone was
based on the following considerations: leg fractures are
very common, and excluding those due to bone fragility
from osteoporosis ensure that the frequency of delayed
healing is sufficiently high to provide concrete data. Furthermore, considering more fracture sites would have
involved a significant increase in the number of variables
and patients analyzed.
The L-ARRCO values were correlated with healing time
(r = ?0.40); however, the sensitivity of the score was not
satisfactory, as although a significant number of patients
obtained a low score, their healing times showed an
extremely wide range. In fact, the ROC curve gave an AUC
that was not particularly high (0.62 0.09), which implies
that the sensitivity and specificity of the score would not be
satisfactory at any point on the curve. A cluster of patients
with scores ranging between four and six who took longer
than 180 days to heal were responsible for this low
sensitivity.
However, data collected from the patients hospital
records allowed other parameters associated with delayed
healing to be identified and used in a second score, named

J Orthopaed Traumatol (2013) 14:5157

55

Fig. 1 Analysis of the

correlation between clinical
healing time and L-ARRCO
score

Table 4 Parameters associated with prolonged healing time

Parameter

ARRCO. Satisfactory values of sensitivity (82 %) and

specificity (70 %) were obtained with ARRCO. In addition,
the correlation of the ARRCO score values with fracture
healing time (r = ?0.69) was significantly better than seen
for the previous score.
The main limitation of this study is that it is a retrospective analysis and includes a limited number of patients.
However, this study clearly demonstrates, as a proof of
principle, that a complete and balanced evaluation of the
various risks present at the time of fracture can reliably
identify the majority of the patients who may suffer prolonged healing times.

Confidence
interval 95 %

Malnutrition

4.1

Tibia fracture without fibia involvement

1.6

1.04.8

Loss of bone substance

4.0

1.115.8

Graft with saw bone

Fig. 2 Box plot of the L-ARRCO scores for the two groups analyzed:
\180 days (patient healed), [180 days (patient suffered delayed
healing). The horizontal line in the box indicates the median, the box
indicates the standard deviation, and the vertical bars indicate the
confidence interval at 95 %. The p value indicates the comparison
between the two groups using Students t test

Relative
risk

1.348.4

12.3

1.3114.6

Plate ? diastasis

6.0

1.034.4

Plate ? instability
Locking compression plate

3.2
2.8

1.020.8
1.210.8

Plate ? blood loss

4.4

1.216.1

Plate ? plastera

0.9

0.31.0

Age (age classes)

1.2

1.02.3

Obesity

1.5

1.17.5

Smoking

3.0

1.49.9

Type of fracture (closed;

exposed \ 5 cm; exposed [ 5 cm,
open grade I)
Localization (diaphysis;
epiphysis-metaphysis)

2.0

1.13.8

3.1

1.310.0

Instability

1.8

1.15.5

Diastasis

1.4

1.04.2

Alignmenta

0.4

0.00.8

Treatment (conservative; plate;

endomedullary nail; external fixator)

7.9

2.525.3

Table shows parameters associated with prolonged healing time

a

Associated with reduced risk

This study has identified relevant informationclinical

and associated with surgerythat should be collected in a
prospective study. Using power analysis, it has been calculated that the number of patients required for such a
prospective study would be 300. Performing such a

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Fig. 3 Analysis of the

correlation between clinical
healing time and ARRCO score

Fig. 4 Box plot of the ARRCO scores for the two groups analyzed:
\180 days (patient healed), [180 days (patient suffered delayed
healing). The horizontal line in the box indicates the median, the box
indicates the standard deviation, and the vertical bars indicate the
confidence interval at 95 %. The p value indicates the comparison
between the two groups using Students t test

prospective study would lead to the identification of multiple conditions that influence the process of fracture
healing, alone and in combination, and would allow their
importance to be assessed. Therefore, a reliable score to
estimate the risk gradient for prolonged fracture healing
time could be developed.
The software available could easily be adapted and used
in orthopedic practice. After reliably calculating the predicted risk of delayed healing, the orthopedic surgeon
could prescribe therapy that can be applied earlier than is
currently the case, for example favoring osteogenetic
activity using systemic or local drug therapy, or by

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Fig. 5 ROC curve for discriminating subjects with healing times of

\180 days from subjects who suffered delayed healing

stimulating the endogenous synthesis of bone morphogenetic proteins using physical stimuli. The identification and
selection of fractures at risk using ARRCO also represents
an important study tool, as it makes it possible to test and
focus the study of new therapeutic interventions on a
limited but specific number of patients, as well as to assess
treatment costs for fractures at risk.
Conflict of interest Francesca de Terlizzi and Stefania Setti are
IGEA SpA employers. The ARRCO software was produced by IGEA
SpA and was provided free of charge to the centers involved in the
study. All authors declare that they have no competing interests.

J Orthopaed Traumatol (2013) 14:5157

Open Access This article is distributed under the terms of the
Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original
author(s) and the source are credited.

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